Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts
Abstract
β-Cells generated from large-scale sources can overcome current shortages in clinical islet cell grafts provided that they adequately respond to metabolic variations. Pancreatic (non)endocrine cells can develop from human embryonic stem (huES) cells following in vitro derivation to pancreatic endoderm (PE) that is subsequently implanted in immune-incompetent mice for further differentiation. Encapsulation of PE increases the proportion of endocrine cells in subcutaneous implants, with enrichment in β-cells when they are placed in TheraCyte-macrodevices and predominantly α-cells when they are alginate-microencapsulated. At posttransplant (PT) weeks 20-30, macroencapsulated huES implants presented higher glucose-responsive plasma C-peptide levels and a lower proinsulin-over-C-peptide ratio than human islet cell implants under the kidney capsule. Their ex vivo analysis showed the presence of single-hormone-positive α- and β-cells that exhibited rapid secretory responses to increasing and decreasing glucose concentrations, similar to isolated human islet cells. However, their insulin secretory amplitude was lower, which was attributed in part to a lower cellular hormone content; it was associated with a lower glucose-induced insulin biosynthesis, but not with lower glucagon-induced stimulation, which together is compatible with an immature functional state of the huES-derived β-cells at PT weeks 20-30. These data support the therapeutic potential of macroencapsulated huES implant…
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Macroencapsulation devices have had success in preventing overt immune rejection of pancreatic tissue.
“While these devices have had success in preventing overt immune rejection of pancreatic tissue,”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [88]
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- Authors
- Motté, E., Szepessy, E., Suenens, K., Stangé, G., Bomans, M., Jacobs-Tulleneers-Thevissen, D., Ling, Z., Kroon, E., Pipeleers, D., & Beta Cell Therapy Consortium EU-FP7
- Affiliations
- Vrije Universiteit Brussel (BE)
- Beta-Cell NV, Brussels, Belgium; and
- Diabetes Research Center, Brussels Free University-Vrije Universiteit Brussel, Brussels, Belgium;
- ViaCyte (United States) (US)
- Corresponding author
- Pipeleers, Daniel
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2014-11-01
- Volume
- 307
- Issue
- 9
- Pages
- E838-E846
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2011702432
- Cited by
- 100
- References
- 35
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 13 · 2019: 10 · 2018: 10 · 2017: 15 · 2016: 14 · 2015: 8
- FWCI
- 12.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Vrije Universiteit Brussel
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- human embryonic stem cells, macroencapsulation, beta cell differentiation, alginate microencapsulation, glucose-stimulated insulin secretion, C-peptide, proinsulin, glucagon, insulin biosynthesis, type 1 diabetes
- MeSH terms
- Animals, C-Peptide, Cell Differentiation, Cell Line, Crosses, Genetic, Diabetes Mellitus, Type 1, Humans, Kidney, Membranes, Proinsulin, Transplantation, Heterologous, Transplantation, Heterotopic, Islets of Langerhans Transplantation, Mice, SCID, Mice, Inbred NOD, Cells, Immobilized, Implants, Experimental, Subcutaneous Tissue, Glucagon-Secreting Cells, Insulin-Secreting Cells, Embryonic Stem Cells, Tissue Scaffolds
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